Dibutyryl-cyclic GMP induces peripheral antinociception via activation of ATP-sensitive K(+) channels in the rat PGE2-induced hyperalgesic paw.

1. Using the rat paw pressure test, in which increased sensitivity is induced by intraplantar injection of prostaglandin E2, we studied the action of several K(+) channel blockers in order to determine what types of K(+) channels could be involved in the peripheral antinociception induced by dibutyrylguanosine 3 : 5'-cyclic monophosphate (DbcGMP), a membrane permeable analogue of cyclic GMP. 2. DbcGMP elicited a dose-dependent (50, 75, 100 and 200 microg paw(-1)) peripheral antinociceptive effect. The effect of the 100 microg dose of DbcGMP was considered to be local since only a higher dose (300 microg paw(-1)) produced antinociception in the contralateral paw. 3. The antinociceptive effect of DbcGMP (100 microg paw(-1)) was dose-dependently antagonized by intraplantar administration of the sulphonylureas tolbutamide (20, 40 and 160 microg) and glibenclamide (40, 80 and 160 microg), selective blockers of ATP-sensitive K(+) channels. 4. Charybdotoxin (2 microg paw(-1)), a selective blocker of high conductance Ca(2+)-activated K(+) channels, and apamin (10 microg paw(-1)), a selective blocker of low conductance Ca(2+)-activated K(+) channels, did not modify the peripheral antinociception induced by DbcGMP. 5. Tetraethylammonium (2 mg paw(-1)), 4-aminopyridine (200 microg paw(-1)) and cesium (800 paw(-1)), non-selective voltage-gated potassium channel blockers, also had no effect. 6. Based on this experimental evidence, we conclude that the activation of ATP-sensitive K(+) channels could be the mechanism by which DbcGMP induces peripheral antinociception, and that Ca(2+)-activated K(+) channels and voltage-dependent K(+) channels appear not to be involved in the process.